Symptomatic Gastroesophageal Reflux Disease (sGERD)
Conditions
Keywords
Gastroesophageal Reflux Disease, GERD
Brief summary
The purpose of this study is to compare the efficacy, safety and tolerability of rabeprazole extended release (ER) 50 mg with placebo in subjects with symptomatic gastroesophageal reflux disease (sGERD).
Interventions
DRUGrabeprazole sodium
One rabeprazole extended release (ER) 50 mg capsule daily; rescue medication will be provided to subjects to take as needed.
DRUGPlacebo
One rabeprazole placebo capsule daily; rescue medication will be provided to subjects to take as needed.
Sponsors
Eisai Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
KEY INCLUSION CRITERIA: Male or female, ages 18 through 75 years will be included in the study. Females should be either of nonchildbearing potential or of childbearing potential. Females of childbearing potential must have negative serum and urine pregnancy tests prior to randomization. Female subjects of childbearing potential must agree to use medically acceptable methods of contraception starting at Visit 1 and throughout the entire study period and for 1 month after the last dose of study drug. Women using hormonal contraceptives must also be using an additional approved method of contraception starting at Visit 1 and throughout the entire study period and for 1 month after the last dose of study drug. Pregnant or lactating females are excluded. Subjects must have a history of heartburn, identified as their main complaint, for 6 months or longer.Subjects must have documentation of a minimum of 5 moderate to severe heartburn episodes, 3 of which occur during the daytime and 1 of which occurs during the nighttime, during the last 7 days before randomization. Subjects must be able to read, write, and understand the language of the symptom dairy. KEY
Exclusion criteria
Subjects will be excluded from the study if they are found to have erosive esophagitis during esophagogastroduodenoscopy (EGD) at Screening, current or a history of esophageal motility disorders, current or a history of Barrett's esophagus, current esophageal strictures or esophagitis (known or suspected to be due to etiology other than GERD such as infection or medications), current or a history of Zollinger-Ellison syndrome and acid hypersecretory conditions, or current gastric or duodenal ulcer. Subjects will be excluded if they are found to have current or a history of cancer, with the exception of fully excised skin basal cell carcinoma, inflammatory bowel disease, a history of esophageal, gastric and duodenal surgery, except simple closure of a perforated ulcer. Subjects will be excluded who require daily use of nonsteroidal anti-inflammatory drugs (NSAIDs), oral steroids (\>=20 mg/day prednisone or equivalent), or aspirin (\>325 mg/day). Female subjects will be excluded who are pregnant, lactating, or have a positive B-human gonadotropin test at Screening/Baseline. Subjects will be excluded who are known to be human immunodeficiency virus (HIV) positive, have participated in another investigational drug study within 30 days prior to screening or are expected to receive an investigational drug during this trial. Subjects who are unwilling to provide informed consent will be excluded.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Percentage of Diary-Recorded Heartburn-Free Days at Week 4 | Week 4 | Participants completed a daily symptom diary. A heartburn-free day was defined as participant report of 'No Heartburn' from nighttime and daytime of the diary for the same day. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Average Daily Severity Score of Gastroesophageal Reflux Disease (GERD)-Related Symptoms at Week 4 | Baseline and Week 4 | Participants collected GERD-associated symptoms of daytime heartburn, nighttime heartburn and regurgitation in daily symptom diary. Daytime episodes were defined as those that occurred after arising in the morning until retiring in the evening, and nighttime episodes were defined as those that occurred during the night while sleeping or trying to sleep. The severity score was calculated was based on a 5-point Likert scale ranging from 0 (no symptom) to 4 (very severe symptom); higher scores indicated greater disease activity. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Complete Heartburn Relief | Week 2 and Week 4 | Participants completed a daily symptom diary. |
| Time to Achieve First 24-Hour Period Without Heartburn | Baseline to Week 4 | Participants completed a daily symptom diary. |
Countries
United States
Participant flow
Pre-assignment details
Out of the 305 participants who were enrolled into the study, 300 participants received the study treatment.
Participants by arm
| Arm | Count |
|---|---|
| Placebo One placebo capsule, orally, each day for 4 weeks, identical in appearance to the RAB (Rabeprazole) ER (Extended Release) 50mg capsule | 147 |
| RAB ER 50mg One RAB ER 50mg capsule, orally, each day for 4 weeks | 153 |
| Total | 300 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 4 |
| Overall Study | Lack of Efficacy | 4 | 1 |
| Overall Study | Lost to Follow-up | 2 | 4 |
| Overall Study | Other | 2 | 2 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
| Overall Study | Withdrawal of consent | 1 | 4 |
Baseline characteristics
| Characteristic | Placebo | RAB ER 50mg | Total |
|---|---|---|---|
| Age, Continuous | 44.4 Years STANDARD_DEVIATION 13.32 | 43.8 Years STANDARD_DEVIATION 12.35 | 44.1 Years STANDARD_DEVIATION 12.82 |
| Sex: Female, Male Female | 103 Participants | 105 Participants | 208 Participants |
| Sex: Female, Male Male | 44 Participants | 48 Participants | 92 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 147 | 0 / 152 |
| serious Total, serious adverse events | 1 / 147 | 0 / 152 |
Outcome results
Primary
Mean Percentage of Diary-Recorded Heartburn-Free Days at Week 4
Participants completed a daily symptom diary. A heartburn-free day was defined as participant report of 'No Heartburn' from nighttime and daytime of the diary for the same day.
Time frame: Week 4
Population: Intent-to-Treat (ITT) Population - all randomized participants who received at least 1 dose of study drug (n=number of participants with evaluable data)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Percentage of Diary-Recorded Heartburn-Free Days at Week 4 | 21.23 Percentage of Days | Standard Deviation 26.8 |
| RAB ER 50mg | Mean Percentage of Diary-Recorded Heartburn-Free Days at Week 4 | 41.14 Percentage of Days | Standard Deviation 34.49 |
Secondary
Change From Baseline in Average Daily Severity Score of Gastroesophageal Reflux Disease (GERD)-Related Symptoms at Week 4
Participants collected GERD-associated symptoms of daytime heartburn, nighttime heartburn and regurgitation in daily symptom diary. Daytime episodes were defined as those that occurred after arising in the morning until retiring in the evening, and nighttime episodes were defined as those that occurred during the night while sleeping or trying to sleep. The severity score was calculated was based on a 5-point Likert scale ranging from 0 (no symptom) to 4 (very severe symptom); higher scores indicated greater disease activity.
Time frame: Baseline and Week 4
Population: ITT
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Average Daily Severity Score of Gastroesophageal Reflux Disease (GERD)-Related Symptoms at Week 4 | Heartburn (Daytime) | -0.82 Scores on a Scale | Standard Deviation 0.65 |
| Placebo | Change From Baseline in Average Daily Severity Score of Gastroesophageal Reflux Disease (GERD)-Related Symptoms at Week 4 | Heartburn (Nighttime) | -0.74 Scores on a Scale | Standard Deviation 0.72 |
| Placebo | Change From Baseline in Average Daily Severity Score of Gastroesophageal Reflux Disease (GERD)-Related Symptoms at Week 4 | Regurgitation | -0.49 Scores on a Scale | Standard Deviation 0.62 |
| RAB ER 50mg | Change From Baseline in Average Daily Severity Score of Gastroesophageal Reflux Disease (GERD)-Related Symptoms at Week 4 | Heartburn (Daytime) | -1.22 Scores on a Scale | Standard Deviation 0.79 |
| RAB ER 50mg | Change From Baseline in Average Daily Severity Score of Gastroesophageal Reflux Disease (GERD)-Related Symptoms at Week 4 | Heartburn (Nighttime) | -1.17 Scores on a Scale | Standard Deviation 0.78 |
| RAB ER 50mg | Change From Baseline in Average Daily Severity Score of Gastroesophageal Reflux Disease (GERD)-Related Symptoms at Week 4 | Regurgitation | -0.74 Scores on a Scale | Standard Deviation 0.81 |
Other Pre-specified
Percentage of Participants With Complete Heartburn Relief
Participants completed a daily symptom diary.
Time frame: Week 2 and Week 4
Population: ITT (n=number of participants with evaluable data)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Complete Heartburn Relief | Week 2 (n=147, 148) | 3.4 Percentage of Participants |
| Placebo | Percentage of Participants With Complete Heartburn Relief | Week 4 (n=147, 148) | 7.5 Percentage of Participants |
| RAB ER 50mg | Percentage of Participants With Complete Heartburn Relief | Week 2 (n=147, 148) | 15 Percentage of Participants |
| RAB ER 50mg | Percentage of Participants With Complete Heartburn Relief | Week 4 (n=147, 148) | 22.2 Percentage of Participants |
Other Pre-specified
Time to Achieve First 24-Hour Period Without Heartburn
Participants completed a daily symptom diary.
Time frame: Baseline to Week 4
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Time to Achieve First 24-Hour Period Without Heartburn | 14.4 Days | Standard Error 0.84 |
| RAB ER 50mg | Time to Achieve First 24-Hour Period Without Heartburn | 10.6 Days | Standard Error 0.92 |